S4865 A Rash Decision: Unraveling Sulfasalazine-Induced Hypersensitivity Syndrome in a Patient With Crohn’s Disease

Introduction: Sulfasalazine-induced hypersensitivity syndrome (SIHS) is a rare but potentially life-threatening reaction to sulfasalazine (SSZ), a medication commonly used for inflammatory bowel disease. SIHS often presents with systemic symptoms including fever, skin rash, and liver dysfunction several weeks after initiation. We report a case of SIHS in a patient recently started on SSZ for Crohn’s disease, highlighting the need for early recognition and intervention. Case Description/Methods: A 68-year-old man with newly diagnosed Crohn’s disease presented with fever, altered mental status, and a diffuse maculopapular rash with skin sloughing. Initial labs showed mild leukocytosis without eosinophilia or atypical lymphocytes and significantly elevated liver function tests, prompting a Gastroenterology consultation. A comprehensive infectious, metabolic, and autoimmune workup was negative. Abdominal imaging was largely unremarkable with hepatic steatosis, hepatomegaly, and cholelithiasis. Liver biopsy revealed moderate nonspecific lobular and portal inflammation. Given SSZ initiation 4 weeks prior, SIHS was suspected. Discontinuing SSZ led to rapid improvement in both the rash and liver function tests, further confirming the diagnosis. As symptoms improved without further intervention, corticosteroids were not needed, and the patient was discharged in stable condition. Discussion: SSZ consists of 5-ASA and sulfapyridine. While 5-ASA exerts anti-inflammatory effects locally in the colon, sulfapyridine is absorbed and metabolized in the liver, driving its systemic effects. SIHS is thought to result from type IV delayed hypersensitivity reaction and genetic predisposition, with HLA-B08:01 and HLA-A31:01 associated with increased risk. Some cases are also linked to HHV-6 reactivation and reduced N-acetyltransferase activity. SIHS commonly presents with fever, skin rash, and in 4% of cases, liver toxicity. Diagnosis requires exclusion of alternative causes and symptom resolution after SSZ discontinuation. Management includes prompt SSZ cessation, with corticosteroids and intravenous immunoglobulin reserved for severe cases. To minimize risks of SIHS, localized formulation such as rectal SSZ or pure 5-ASA such as Mesalamine can be used. Since re-exposure to SSZ can lead to increased severity of SIHS, early diagnosis and intervention are crucial for favorable outcomes. Clinicians should therefore maintain a high index of suspicion for SIHS in patients with systemic symptoms shortly after starting SSZ.